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Therapeutic Application

Capturing the different health conditions that PAP may adress

Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy.

April 3, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

A growing body of evidence shows that existential and spiritual well-being in cancer patients is associated with better medical outcomes, improved quality of life, and serves as a buffer against depression, hopelessness, and desire for hastened death. Historical and recent research suggests a role for psilocybin-assisted psychotherapy in treating cancer-related anxiety and depression. A double-blind controlled trial was performed, where 29 patients with cancer-related anxiety and depression were randomly assigned to treatment with single-dose psilocybin (0.3 mg/kg) or niacin in conjunction with psychotherapy. Previously published results of this trial demonstrated that, in conjunction with psychotherapy, moderate-dose psilocybin produced rapid, robust, and enduring anxiolytic, and anti-depressant effects. Here, we illustrate unique clinical courses described by four participants using quantitative measures of acute and persisting effects of psilocybin, anxiety, depression, quality of life, and spiritual well-being, as well as qualitative interviews, written narratives, and clinician notes. Although the content of each psilocybin-assisted experience was unique to each participant, several thematic similarities and differences across the various sessions stood out. These four participants’ personal narratives extended beyond the cancer diagnosis itself, frequently revolving around themes of self-compassion and love, acceptance of death, and memories of past trauma, though the specific details or narrative content differ substantially. The results presented here demonstrate the personalized nature of the subjective experiences elicited through treatment with psilocybin, particularly with respect to the spiritual and/or psychological needs of each patient.
Malone, T. C., Mennenga, S. E., Guss, J., Podrebarac, S. K., Owens, L. T., Bossis, A. P., … & Ross, S. (2018). Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy. Frontiers in pharmacology, 9, 256, 10.3389/fphar.2018.00256
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Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine

April 2, 2018 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants’ OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.
Malcolm, B. J., Polanco, M., & Barsuglia, J. P. (2018). Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine. Journal of psychoactive drugs, 1-10. 10.1080/02791072.2018.1447175
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Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression

March 30, 2018 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Natural speech analytics has seen some improvements over recent years, and this has opened a window for objective and quantitative diagnosis in psychiatry. Here, we used a machine learning algorithm applied to natural speech to ask whether language properties measured before psilocybin for treatment-resistant can predict for which patients it will be effective and for which it will not.
METHODS:
A baseline autobiographical memory interview was conducted and transcribed. Patients with treatment-resistant depression received 2 doses of psilocybin, 10 mg and 25 mg, 7 days apart. Psychological support was provided before, during and after all dosing sessions. Quantitative speech measures were applied to the interview data from 17 patients and 18 untreated age-matched healthy control subjects. A machine learning algorithm was used to classify between controls and patients and predict treatment response.
RESULTS:
Speech analytics and machine learning successfully differentiated depressed patients from healthy controls and identified treatment responders from non-responders with a significant level of 85% of accuracy (75% precision).
CONCLUSIONS:
Automatic natural language analysis was used to predict effective response to treatment with psilocybin, suggesting that these tools offer a highly cost-effective facility for screening individuals for treatment suitability and sensitivity.
LIMITATIONS:
The sample size was small and replication is required to strengthen inferences on these results.
Carrillo, F., Sigman, M., Slezak, D. F., Ashton, P., Fitzgerald, L., Stroud, J., … & Carhart-Harris, R. L. (2018). Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression. Journal of affective disorders, 230, 84-86. 10.1016/j.jad.2018.01.006
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Ceremonial ‘Plant Medicine’ use and its relationship to recreational drug use: an exploratory study

March 30, 2018 / Ayahuasca, Biology & Ethnobotany, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Background: The ceremonial use of psychoactive/hallucinogenic plant based drugs, such as ayahuasca, psilocybin and others, is a growing trend in the United States (US) and globally. To date, there has been little research documenting how many people are using psychoactive substances in this context, who the users are, what benefits/risks exist in the use of these drugs and the relationship between ceremonial drug use and recreational drug use.
In this paper we describe a cohort of plant medicine facilitators in the US and explore how they differentiate plant medicine use from recreational drug use.
Methods: Using modified ethnography, individual interviews were conducted in 2016 with 15 participants who are currently facilitating plant medicine ceremonies in the US. Descriptive content analysis was performed to discover themes and to inform a larger mixed-method study.
Results: Ceremonial drug use was seen by participants as a natural healing and treatment modality used in the context of community and ritual. Three main themes were identified relating to participants’ differentiation between ceremonial plant medicine use and recreational drug use: (1) participants see a clear delineation between plant medicine use and recreational drug use; (2) plant medicine is seen as a potential treatment for addiction, but concerns exist regarding potential interference with recovery; and (3) plant medicine use may influence recreational use.
Conclusions: More research is needed on who is using plant medicine, motivators for use, perceived and real risks and benefits of plant medicine use and harm reduction techniques regarding safe ingestion.
Dorsen, C., Palamar, J., & Shedlin, M. G. (2018). Ceremonial ‘Plant Medicine’use and its relationship to recreational drug use: an exploratory study. Addiction Research & Theory, 1-8. 10.1080/16066359.2018.1455187
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Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature

March 23, 2018 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , ,

Abstract

INTRODUCTION:
Over the past decade, ketamine has been studied for major depressive disorder and bipolar depression. Ketamine is believed to exert its antidepressant properties through N-methyl-D-aspartate receptor antagonism.
METHODS:
Study authors completed a literature review of seven randomized controlled trials of ketamine usage in major depressive disorder and bipolar depression.
RESULTS:
Ketamine demonstrated a statistically significant improvement over placebo or midazolam in major depressive disorder. Ketamine also exhibited a statistically significant improvement over placebo in bipolar depression.
DISCUSSION:
Ketamine has shown promise in quickly reducing symptoms in patients with treatment resistant depression and bipolar depression. Using ketamine may be helpful for patients that have exhausted other therapeutic options.
Grady, S. E., Marsh, T. A., Tenhouse, A., & Klein, K. (2017). Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature. Mental Health Clinician, 7(1), 16-23. 10.9740/mhc.2017.01.016
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Out of the box: A psychedelic model to study the creative mind

March 23, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Publications / By /

Abstract

Our creativity is challenged daily when facing new situations asking for novel solutions. Creativity, a multicomponent construct includes flexible divergent and rigid convergent thinking. Psychedelic drugs like psilocybin can enhance creativity and affect state of mind (mood, empathy, openness). Of note, flexible thinking is disturbed in psychopathological conditions like anxiety disorders and depression and preliminary findings have shown psychedelics to be efficacious in the treatment of those conditions. The question how psychedelics induce this state of enhanced flexible thinking remains to be answered and investigating the neurobiology underlying this phenomenon will not only help in understanding why psychedelics are of use in the therapeutic setting but also in other settings where flexible thinking is challenged. A model including neuronal networks, neurotransmitters and personal factors playing a role in this process will be proposed which can be put to the test by means of placebo-controlled pharmaco-imaging studies in healthy volunteers.

Kuypers, K. P. C. (2018). Out of the box: A psychedelic model to study the creative mind. Medical hypotheses, 115, 13-16.,  10.1016/j.mehy.2018.03.010

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Role of the 5-HT2A receptor in self- and other-initiated social interaction in LSD-induced states – a pharmacological fMRI study

March 19, 2018 / LSD, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , ,

Abstract

Distortions of self-experience are critical symptoms of psychiatric disorders and have detrimental effects on social interactions. In light of the immense need for improved and targeted interventions for social impairments, it is important to better understand the neurochemical substrates of social interaction abilities. We therefore investigated the pharmacological and neural correlates of self- and other-initiated social interaction. In a double-blind, randomized, counterbalanced, cross-over study 24 healthy human participants (18 males and 6 females) received either 1) placebo+placebo 2) placebo+lysergic acid diethylamide (LSD) (100 μg p.o.), or 3) ketanserin (40 mg p.o.)+LSD (100 μg p.o.) at three different occasions. Participants took part in an interactive task using eye-tracking and functional magnetic resonance imaging completing trials of self- and other-initiated joint and non-joint attention. Results demonstrate first, that LSD reduced activity in brain areas important for self-processing, but also social cognition, second that change in brain activity was linked to subjective experience, and third that LSD decreased the efficiency of establishing joint attention. Furthermore, LSD-induced effects were blocked by the serotonin 2A receptor (5-HT2AR) antagonist ketanserin, indicating that effects of LSD are attributable to 5-HT2AR stimulation. The current results demonstrate that activity in areas of the ‘social brain’ can be modulated via the 5-HT2AR thereby pointing towards this system as a potential target for the treatment of social impairments associated with psychiatric disorders.SIGNIFICANCE STATEMENTDistortions of self-representation and, potentially related to this, dysfunctional social cognition are central hallmarks of various psychiatric disorders and critically impact disease development, progression, treatment, as well as real-world functioning. However, these deficits are insufficiently targeted by current treatment approaches. The administration of lysergic acid diethylamide (LSD) in combination with functional magnetic resonance imaging and real-time eye-tracking offers the unique opportunity to study alterations in self-experience, their relation to social cognition, and the underlying neuropharmacology. Results demonstrate that LSD alters self-experience as well as basic social cognition processing in areas of the ‘social brain’. Furthermore, these alterations are attributable to 5-HT2A receptor stimulation, thereby pinpointing towards this receptor system in the development of pharmacotherapies for sociocognitive deficits in psychiatric disorders.
Preller, K. H., Schilbach, L., Pokorny, T., Flemming, J., Seifritz, E., & Vollenweider, F. X. (2018). Role of the 5-HT2A receptor in self-and other-initiated social interaction in LSD-induced states—a pharmacological fMRI study. Journal of Neuroscience, 1939-17. 10.1523/JNEUROSCI.1939-17.2018
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Repeated intranasal ketamine for treatment-resistant depression – the way to go? Results from a pilot randomised controlled trial

March 15, 2018 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments.
METHODS:
This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment.
RESULTS:
Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (>45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups.
CONCLUSIONS:
IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD.
Gálvez, V., Li, A., Huggins, C., Glue, P., Martin, D., Somogyi, A. A., … & Loo, C. K. (2018). Repeated intranasal ketamine for treatment-resistant depression–the way to go? Results from a pilot randomised controlled trial. Journal of Psychopharmacology, 32(4), 397-407. 10.1177/0269881118760660
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Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action

March 13, 2018 / Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Recent, well-controlled – albeit small-scale – clinical trials show that serotonergic psychedelics, including psilocybin and lysergic acid diethylamide, possess great promise for treating psychiatric disorders, including treatment-resistant depression. Additionally, fresh results from a deluge of clinical neuroimaging studies are unveiling the dynamic effects of serotonergic psychedelics on functional activity within, and connectivity across, discrete neural systems. These observations have led to testable hypotheses regarding neural processing mechanisms that contribute to psychedelic effects and therapeutic benefits. Despite these advances and a plethora of preclinical and clinical observations supporting a central role for brain serotonin 5-HT2A receptors in producing serotonergic psychedelic effects, lingering and new questions about mechanisms abound. These chiefly pertain to molecular neuropharmacology. This chapter is devoted to illuminating and discussing such questions in the context of preclinical experimental approaches for studying mechanisms of action of serotonergic psychedelics, classic and new.

Canal, C. E. (2018). Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action. 10.1007/164_2018_107
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Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats

March 13, 2018 / Anxiety Disorders / PTSD, Ketamine, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

Short-term moderate doses of serotonergic and dissociative hallucinogens can be useful in the treatment of anxiety. Recently, a trend has developed for long-term intermittent ‘microdosing’ (usually one-tenth of a ‘full’ active dose), with reports of long-lasting relief from anxiety and related disorders; however, there is no scientific evidence for the efficacy of therapeutic microdosing nor to show its lasting effects. The objective of this study was to test for lasting effects on anxiety in rats after microdosing with ketamine or psilocin. Over 6 days, Wistar rats (N=40) were administered ketamine (0.5 or 3 mg/kg), psilocin (0.05 or 0.075 mg/kg), or saline on three occasions. A 5-min elevated plus-maze test was conducted 48 h after the final drug treatment (n=8). Dependent variables were entries (frequency), spent time (%), and distance traveled (cm) in each zone, as well as total frequency of rears, stretch-attend postures, and head dips. Statistical analyses of drug effects used separate independent one-way analysis of variance and pair-wise comparisons using independent t-tests. Statistical effects were modest or borderline and were most consistent with a mildly anxiogenic profile, which was significant at lower doses; however, this conclusion remains tentative. The lower doses of ketamine and psilocin produced comparable effects (to one another) across each variable, as did the higher doses. This pattern of effects may suggest a common (e.g. neurotransmitter/receptor) mechanism. We conclude that microdosing with hallucinogens for therapeutic purposes might be counter-productive; however, more research is needed to confirm our findings and to establish their translational relevance to clinical ‘psychedelic’ therapy.
Horsley, R. R., Páleníček, T., Kolin, J., & Valeš, K. (2018). Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats. Behavioural pharmacology. 10.1097/FBP.0000000000000394
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